Current progress from this laboratory has indicated that endotoxin administration impairs myocardial metabolism by two different mechanisms: one by acting through membrane lipid microenvironment and the other by affecting protein phosphorylation/dephosphorylation. The primary aims of this proposal are to continue our search for the understanding of pathophysiology of myocardial dysfunction at the cellular level and, ultimately, to propose a rational remedy for the better management of shock. The specific objectives include studies of phosphorylaton/dephosphorylation of cardiac sarcolemma and sarcoplasmic reticulum in relationship to membrane enzyme and receptor dynamics; investigation of phosphorylation/dephosphorylation of contractile proteins and its association with myofibrillar ATPase activities; studies of the biological activity of calmodulin and the Ca2+ binding properties of calmodulin and triponin C; analysis of the chemical structure and physical properties of myocyte membrane lipids; studies of myocyte-liposome interactions; and development of a liposome preparation to be used as a membrane modifier and as a drug carrier system for the therapeutic interventions of endotoxin shock.